Physical Sciences Inc. has successfully completed a Phase I program that demonstrated the feasibility of three-dimensional tracking for motion stabilization. The developed system extends the capabilities of our patented, high-speed, non-imaging tracker specifically for optical coherence tomography (OCT) based diagnostic technology. For ophthalmic applications, the three-dimensional tracker will obviate the need for complicated post-processing image registration algorithms currently used in commercial clinical OCT systems. Moreover, the tracking system will improve state-of-the-art spectral domain OCT (SDOCT) and optical Doppler tomography (ODT and SDODT) systems for the measurement of retinal blood flow in the smallest capillaries with improved phase stability and a wider dynamic range. The system will enable unprecedented resolution of retinal structures, creation of speckle and noise-reduced composite images by averaging hundreds of images, the generation of high-resolution three-dimensional maps, and the ability to return to the exact same tissue location days, months, or years later. We propose herein to continue the development of the three-dimensional tracker in a Phase II program. The optical setup will be moved from the bench-top to a compact optical head mounted to a standard chin rest for retinal imaging. The instrumentation will likewise be moved from the laboratory to a small portable clinical cart. Other extensive optical, electronic, and mechanical modifications will make the system easy-to-use and easily modified for clinical technicians and researchers alike. The system will be tested for two applications. First and foremost, the system will be tested in human volunteers and the primary application will be ophthalmic diagnosis of retinal diseases, included defects in perfusion, where current techniques are limited by eye motion. Second, the system will be tested during in vivo imaging of the innominate artery of a genetically altered mouse for the specific research application of the identification and characterization of vulnerable plaque in coronary artery disease. Since the innominate artery lies directly over the heart, this investigation has been especially confounded by motion artifact. The progress made in Phase II will significantly enhance the tools ophthalmologist and researchers have at their disposal for in vivo diagnosis and treatment of a wide variety of diseases.